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Article Dans Une Revue Biochimica et Biophysica Acta - Molecular Cell Research Année : 2018

Novel short isoforms of adenylyl cyclase as negative regulators of cAMP production

Résumé

Here, we cloned a new family of four adenylyl cyclase (AC) splice variants from interleukin-1β (IL-1β)-transdifferentiated vascular smooth muscle cells (VSMCs) encoding short forms of AC8 that we have named "AC8E-H". Using biosensor imaging and biochemical approaches, we showed that AC8E-H isoforms have no cyclase activity and act as dominant-negative regulators by forming heterodimers with other full-length ACs, impeding the traffic of functional units towards the plasma membrane. The existence of these dominant-negative isoforms may account for an unsuspected additional degree of cAMP signaling regulation. It also reconciles the induction of an AC in transdifferentiated VSMCs with the vasoprotective influence of cAMP. The generation of alternative splice variants of ACs may constitute a generalized strategy of adaptation to the cell's environment whose scope had so far been ignored in physiological and/or pathological contexts.
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Dates et versions

hal-02372648 , version 1 (04-12-2019)

Identifiants

Citer

Benjamin Vallin, Yohan Legueux-Cajgfinger, Nathalie Clement, Martine Glorian, Laurent Duca, et al.. Novel short isoforms of adenylyl cyclase as negative regulators of cAMP production. Biochimica et Biophysica Acta - Molecular Cell Research, 2018, 1865 (9), pp.1326-1340. ⟨10.1016/j.bbamcr.2018.06.012⟩. ⟨hal-02372648⟩
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